When Linda Tuttle was diagnosed with breast cancer, she never imagined her experience would inspire her colleagues to design new treatments to tackle the disease.
An administrative assistant in the Department of Chemistry at Wake Forest University, Tuttle was more accustomed to talking to faculty and staff about meetings and course loads – not doctors' appointments and treatment plans.
But after her 2009 diagnosis, Tuttle's use of tamoxifen, a drug commonly used to treat breast cancer, inspired medicinal chemist Ulrich Bierbach to develop a targeted therapy that delivers a sneak attack to the disease, similar to a Trojan horse.
Trojan horses and targeted warheads
Current platinum-based drugs, such as the blockbuster drug cisplatin, do not work on the most common and most difficult-to-cure types of cancer, including lung and breast.
Building upon more than a decade's work in platinum-based drug research, Bierbach's team now designs synthetic hybrid molecules that more effectively tackle otherwise chemo-resistant cancers, including breast cancer. Results of this work, funded by the National Cancer Institute at the National Institutes of Health, appear in the September 13 issue of the Journal of Medicinal Chemistry.
Results also have led to tumor-seeking magic bullets that attach platinum to endoxifen, a close relative of tamoxifen, and quietly hitch a ride to the diseased cells, as if hidden in a Trojan horse.
"Platinum-based drugs cause severe damage to the DNA in cancer cells. Unfortunately, most cancers are smart enough to cut out the DNA damage and repair it, and that's the starting point for our structural design. We developed a compound that does a good job therapeutically by overwhelming the 'damage repair police' of the cell," said Bierbach, a chemistry professor who recently completed a four-year term with the California Breast Cancer Research Program.
Bierbach said that instead of killing certain cancer cells, cisplatin causes kinks in the DNA strand, which prompt cell enzymes to repair the damage. Wake Forest's new platinum-based molecule has a much higher affinity for DNA than cisplatin and twists it in a way that is not easily identified by the cancerous cell.
Initial preclinical studies have proven Bierbach's army of molecules to be 500 times more powerful than cisplatin in treating non-small cell lung cancer, 80-100 times for pancreatic cancer and up to 10 times for breast cancer.
"Within the next two years, we hope to turn our platinum-based drugs into safer, targeted warheads by attaching them to vehicles that will take them to a specific type of cancer and act as a guided missile," he said.
Hope on the horizon
Offering a safer way of delivery will be an important step in convincing industrial partners and the Food and Drug Administration (FDA) to move forward with clinical testing, which Bierbach estimates could be another three to four years away. Still, he and Tuttle remain encouraged given the progress to date.
For nearly three years, they met several times a week to explore Tuttle's treatment options, discuss possible side effects, and defuse her fears.
"My grandmother had breast cancer. We were even the same age when we were diagnosed," said Tuttle. "Now every time I have a strange pain or a headache, I can't help but wonder if I have another tumor."
But unlike her grandmother, whose late stage breast cancer metastasized, Tuttle's cancer was only stage 1 when a routine mammogram detected it. Today she is in remission following a lumpectomy and radiation therapy, and her quality of life has improved.
Though her prognosis looks promising, she and Bierbach still get together frequently in the halls of the chemistry department to share stories – hers of how she now lives every day to its fullest, and his of the lab's progress with its challenging research projects.
"Our professional relationship has definitely grown," said Tuttle. "I hope his research group stays as focused as it is now. Every advancement helps."
"Wake Forest's motto is Pro Humanitate, which means 'for humanity,' and it motivates our research group daily," Bierbach added. "Everyone knows someone who has been affected by cancer, and there's a pressing need for more effective and less toxic chemotherapies. The solution starts with some combination of academic curiosity and personal experience, and takes place in a lab that has synthetic chemistry expertise and a good deal of imagination to think about new ways to tackle cancer mechanistically at the molecular level. It's a fulfilling job, but it's even more rewarding to help someone you know."
Katie Neal | EurekAlert!
Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences
Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University
Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...
On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...
The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...
At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.
When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...
At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.
Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...
16.03.2018 | Event News
13.03.2018 | Event News
08.03.2018 | Event News
16.03.2018 | Earth Sciences
16.03.2018 | Physics and Astronomy
16.03.2018 | Life Sciences